This invention relates to the processes for the preparation of novel [(substituted naphthalenyl)methyl]-3H-1,2,3,5-oxathiadiazole 2-oxides. The compounds have pharmaceutical properties which render them beneficial for the treatment of diabetes mellitus and associated conditions.
The serious complications of diabetes mellitus such as nephropathy, retinopathy, neuropathy and cataract are all associated with an excessive amount of blood glucose. The major therapeutic objective is therefore the normalization of blood glucose, both in the fasting and postprandial situations.
The therapeutic approaches to the treatment of Non-Insulin Dependent Diabetes Mellitus (NIDDM, Type II) involve the use of diet, insulin or orally active hypoglycemic agents. Presently, such agents are chosen (a) from sulfonylureas such as chloropropamide, glyburide and others or (b) biguanides such as metformin and related products. Both these groups of agents have serious disadvantages. Sulfonylureas, upon chronic treatment, lose their effectiveness. In contrast, biguanides suffer from a serious side effect, that causes lactic-acidosis.
More recently, oxazolidinedione (U.S. Pat. No. 4,342,771) and thiazolidinedione (European Patent Application No. 117,035) derivatives have been described as useful hypoglycemic agents. U.S. Pat. No. 4,461,902 discloses substituted 5-[(4-cyclohexyl-methoxyphenyl)methyl]thiazolidine-2,4-diones of formula ##STR1## wherein R is methyl (ciglitazone) and related analogues as hypoglycemic agents.
This invention relates to processes for the production of novel [(substituted naphthalenyl)methyl]-3H-1,2,3,5-oxathiadiazole 2-oxides of the general formula (I): ##STR2## wherein R is hydrogen, lower alkyl containing 1 to 6 carbon atoms, alkoxy containing 1 to 6 carbon atoms, or halogen; and the pharmaceutically acceptable salts thereof having utility as antidiabetic agents.
The oxathiadiazole 2-oxide portion of the compounds of the present invention can exist in more than one tautomeric form. For clarity, only one of the tautomers is represented in the generic formula (I) above. The possible tautomeric forms are listed below: ##STR3##
All of said tautomers are included in the present invention. The actual tautomeric form which the compounds of the present invention assume is not known.
The compounds of this invention are useful as antidiabetic agents for the reduction of blood/plasma sugar levels or for the treatment and/or prevention of diabetic complications and as antihyperlipidemic and antihyperinsulinemic agents.